Association between ultra-processed foods intake with lipid profile: a cross-sectional study

The purpose of this cross-sectional study was to examine the association between ultra-processed foods (UPFs) intake and lipid profile in Iranian people. The study was performed on 236 individuals with the age range of 20–50 years in Shiraz, Iran. Food intakes of the participants were evaluated using a 168-item food frequency questionnaire (FFQ) which was previously validated in Iranian populations. In order to estimate the ultra-processed foods intake, classification of NOVA food group was used. Serum lipids including total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured. The results showed that mean of age and body mass index (BMI) of the participants were 45.98 years and 28.28 kg/m2, respectively. Logistic regression was used to evaluation the relation between UPFs intake and lipid profile. Higher UPFs intake was associated with increased OR of TG and HDL abnormality in both crude (OR 3.41; 95% CI 1.58, 7.34; P-trend = 0.001 and OR 2.99; 95% CI 1.31, 6.82; P-trend = 0.010) and adjusted models (OR 3.69; 95% CI 1.67, 8.16; P-trend = 0.001 and OR 3.38 95% CI 1.42, 8.07; P-trend = 0.009). But, there were no association between UPFs intake and other indices of lipid profile. Also, we found significant associations between UPFs intake and dietary nutrient profiles. In conclusion, UPFs consumption could worsen the nutritional profile of the diet and lead to negative changes in some indices of the lipid profile.


Scientific Reports
| (2023) 13:7258 | https://doi.org/10.1038/s41598-023-34451-x www.nature.com/scientificreports/ chocolate, candies, ice cream, biscuits and cakes; packaged leaves of bread; nugget and sticks, margarine, pastries; pre-prepared food dishes, and many other products 8 . Evidence also showed that high consumption of UPFs is potentially related to the high rate of obesity and related comorbidities 9 . Assessment of UPFs' effects on lipid profiles and upcoming diseases is an ongoing debate. Most studies reported a positive association of UPFs intake with lipid abnormalities, altered blood lipid factors varies in the studies. While, some reported association between UPFs intake with elevated TG and lower HDL-C [10][11][12] , others reported positive association of UPFs consumption with high LDL and total cholesterol 13,14 . As UPFs production and consumption have increased extremely during the last decades, comprehending their potential effects on human health has become a major concern in health care systems. The purpose of this cross-sectional study was to examine the association between UPFs intake and lipid profile in Iranian adults. In addition, as secondary outcomes, we examined the association of UPFs consumption with the intake of food subgroups, macronutrients, and some of the micronutrients. To the best of our knowledge, no previous study has investigated the association between UPFs intake and lipid profile in Iranian adults.

Methods
Study population. This cross-sectional study was performed on 236 individuals with the age range of 20-50 years who were selected by cluster random sampling in health care centers of Shiraz-Iran (Fig. 1). For this purpose, Shiraz was divided in four clusters and one health care center was randomly selected in each cluster. Study sample size was calculated by the following formula, in which α = 0.01, β = 0.10 and r = ± 0.25.
Prerequisites for participating in this study were no history of chronic diseases and no adherence to any special diet (The detailed of this study have been previously published 15,16 ). Written consent form was signed by all participants. The protocol of this study was authorized by Shiraz University of Medical Sciences (IR.SUMS. REC.1394.S146).
Dietary assessment. Food intakes of the participants were evaluated by a 168-item food frequency questionnaire (FFQ) which was previously validated in Iranian populations 17 . The FFQ was filled out based on family food intakes and data was changed to gram. For computing energy, and nutrients intakes we used NUTRITION-IST IV (version 7.0; N-Squared Computing, Salem, OR, USA).
To estimate the ultra-processed foods intake, classification of NOVA food group was used 8,18 . Accordingly, total daily consumption of some foods and beverages items were considered as ultra-processed food (including: packaged breads, buns, confectionaries, pastries and sweets, ice cream, biscuits, cakes, soft drinks, industrial fruit drinks, sweetened milk-based beverages, margarine, sauces, dressings, processed meats, fries, and salty snacks 19 ). To define the contribution of every food group to overall consumption of ultra-processed foods, the mean daily intake of every 9 subgroups of ultra-processed foods (dairy products, non-dairy beverages, margarine and sauces, cakes and cookies, chips and snacks, breads, fast foods and meats, sweets and others) was divided by daily consumption of ultra-processed foods, then multiplied by 100.
Biochemical assessments. Serum lipids including TC, TG, HDL-C and LDL-C were measured in blood samples (5 cm 3 ) taken from the participants commercially accessible enzyme kits (Pars Azmoon, Tehran, Iran).
Socio-demographic and anthropometric assessments. Sex, age, smoking habit and alcohol intake were evaluated by using a questionnaire. Also we used International Physical Activity Questionnaire (IPAQ) 20 to Statistical analysis. All analysis was done using SPSS for windows (version 20.0, SPSS Inc. Chicago IL, USA). The level of significance was P-value < 0.05. Normal distribution of the variables was checked by Kolmogorov-Smirnov test. The relationship between quantitative variables and qualitative variables was evaluated by analysis of variance test and Chi-square test respectively. Crude and adjusted models of logistic regression were used to evaluate the relation between UPFs score with anthropometric index and lipid profile. In adjusted models, the effects of age, energy intake, physical activity, BMI, sex and smoking history were controlled. We dichotomized lipid profile and anthropometric indices then LDL-C more than 130 mg/dL, HDL-C less than 40 mg/dL for male and 50 mg/dL for female, TC more than 200 mg/dL, TG more than 150 mg/dL, non-HDL more than 130 and WC more than 88 cm for female and 102 for male were considered as abnormal 16,21-24 . Ethical approval. The present study was approved by The Research Ethics Committee of Shiraz University of Medical Sciences, Shiraz, Iran (IR.SUMS.REC.1394.S146).
Use of human participants. All experiments were performed in accordance with relevant guidelines and regulations.
Informed consent. All participants singed informed consent form.

Results
As shown in Table 1, mean age and BMI of study population were 45.97 years and 28.28, respectively kg/m 2 . Also, 58.90% of the study participants were female. According to Table 2 there was no significant difference between age, weight, height, BMI, waist circumference, WHR, TC, LDL, HDL, Non-HDL, physical activity, sex, smoking habits, alcohol intake history and education of the participants in the first and last tertile of UPFs, intake, but the difference was significant for mean of serum TG (P = 0.015).
As presented in Table 4, participants in the last tertile of UPFs intake had significantly higher intakes of processed and red meat (P = 0.007) and breads (P = 0.022), also lower intake of margarine and sauces (P < 0.001). There were no differences in non-dairy beverages, cookies and cakes, dairy products, potato chips and salty snacks, sweets and other food items intakes among the UPFs tertiles.

Discussion
We found that higher intake of UPFs was associated with elevated lipid profile abnormality including TG and HDL. In terms of other blood lipids such as TC, LDL and non-HDL, while they were not significantly associate with UPFs intake, all were higher in last tertile of UPFs intake.
In agreement with our study, Lima et al. reported that higher UPFs consumption was associated with higher TG and lower HDL-C levels 25 . Furthermore, a large cohort of older adults in Spain found the same results 10 , and a systematic review and meta-analysis resulted in a negative association between UPFs consumption and HDLcholesterol levels 12 . On the other hand, a cross-sectional study on Ecuadorian adolescents showed that dietary patterns consisted of processed foods were associated with an increased level of LDL and cholesterol 13 . Also, a longitudinal study in Brazil on preschool children found that intake of UPFs was a predictor of higher total Table 4. Daily intakes of UPFs subgroups across the tertiles of UPFs. T tertile, UPFs ultra-processed food.
Values are mean ± (SD). Using one-way ANOVA. Significant values are in bold. www.nature.com/scientificreports/ cholesterol and LDL cholesterol but not HDL and TG probably because effects of food habits on serum LDL and total cholesterol in children are stronger than its effects on other dyslipidemia markers 14 .

UPFs T 1 (n = 95) T 2 (n = 79) T 3 (n = 62) P-value
We found a strong association between the dietary contribution of UPFs and the dietary content of energy, carbohydrates, fat, cholesterol, and SFAs. Moreover, intake of MUFAs and PUFAs increased parallel to UPFs consumption, probably due to high fat content of the UPFs.
With regard to anthropometric indices, although WC and WHR were not significantly associated with UPFs intake, participants in the last tertile of UPFs had higher mean of WC and WHR. Findings of some cohort studies, indicated that higher UPFs intake was associated with greater adiposity accumulation, higher BMI, weight gain and incidence of obesity [26][27][28] . Besides, another cohort study on overweight and obese participants aged 55-75 years reported that higher UPFs intake was associated with higher age-related increase in visceral and overall adiposity 29 . Another similar study also showed a positive association between UPFs intake and the incidence of abdominal obesity in adults 30 . A systematic review and meta-analysis and a multi-national cohort study also reported positive associations between higher consumption of UPFs and general and abdominal obesity 12,31 . We assume that our opposite findings is due to the high mean of our participants' weight, WHR, and WC.
UPFs are often calorie-dense, contain large amounts of fats, saturated fats, trans fats, sodium, and simple sugars with high glycemic index and contain no or small amount of fibers, vitamins, minerals, or other bioactive compounds which naturally exist in fresh foods, so they are nutritionally unbalanced 32 .
Several mechanisms have been suggested to explain the adverse effects of UFPs on lipid profile and health. First of all, due to their intrinsic palatability, overconsumption of UPFs may result in physiological disruption of hunger and satiety patterns [33][34][35][36] . Besides, energy-dense foods usually contain high amounts of free sugar and trans fats which enhance lipogenesis, and decrease fatty acids oxidation which lead to their aggregation in tissues and blood circulation and elevated LDL level 37 . Furthermore, partially hydrogenated vegetable oils content of UPFs contain trans fatty acids which have adverse impacts on lipid profile. In addition, scientific evidence support the hypothesis that the interacting effects of substances produced through the high-heat processing of oils, determine their health effects 38 . Heat processing also causes degradation of food substances and formation of furans in UPFs 39 . Higher intake of UPFs increase exposure to phthalates which is used in the packing process and could transfer to food 40 . The accumulation of phthalates, bisphenols, furans, and their metabolites may ultimately lead to lower HDL-c and elevated TG levels through disruption of endocrine functions 41,42 . Evidence has shown that urinary concentration of phthalates and their metabolites was positively associated with TG and negatively associated with LDL levels 43 .
On the other hand, the impact of carbohydrates on lipid profile also depends on their sources and processing methods. While consumption of free sugar elevates serum TG, whole grains intake decreases TC, LDL and TG levels 44 . Consumption of minimally-processed whole grains such as oatmeal, instead of highly processed refined grains may improve lipid profile 45 .
Our study has some limitations as follows: First, because of the nature of the cross-sectional study, we were not able to assess causal correlations between UPFs intake and lipid profile. In the second place, the study was done in Shiraz city, so it should be generalized to other Iranian adults with caution. Ultimately, although we have removed the effects of some confounders in our analysis, there may be some others which have not been recognized in this study.
In conclusion, our results showed significant associations between ultra-processed foods intake and dietary nutrient profiles which resulted in dyslipidemia as a risk factor for chronic diseases. Findings of the present study highlight a necessity for more evidence, particularly longitudinal, to define the effect of UPFs on lipid profiles.

Data availability
Data available on request from the corresponding author.